1 Research Service, Malcom Randall Department of Veterans Affairs Medical Center , North Florida/South Georgia Veterans Health System, Gainesville, Florida.
2 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.
J Neurotrauma. 2017 Nov 1;34(21):2972-2981. doi: 10.1089/neu.2016.4814. Epub 2017 Jun 5.
We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN; type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week-old male Sprague-Dawley rats received: 1) SHAM surgery (T laminectomy); 2) severe (250 kdyne) contusion SCI; 3) SCI+TE (7.0 mg/week, intramuscular); or 4) SCI+TE+FIN (5 mg/kg/day, subcutaneous). At 8 weeks post-surgery, SCI animals exhibited reduced serum testosterone and levator ani/bulbocavernosus (LABC) muscle mass, effects that were prevented by TE. Cancellous and cortical (periosteal) bone turnover (assessed by histomorphometry) were elevated post-SCI, resulting in reduced distal femur cancellous and cortical bone mass (assessed by microcomputed tomography). TE treatment normalized cancellous and cortical bone turnover and maintained cancellous bone mass at the level of SHAM animals, but produced prostate enlargement. FIN coadministration did not inhibit the TE-induced musculoskeletal effects, but prevented prostate growth. Neither drug regimen prevented SCI-induced cortical bone loss, although no differences in whole bone strength were present among groups. Our findings indicate that TE+FIN prevented the chronic cancellous bone deficits and LABC muscle loss in SCI animals without inducing prostate enlargement, which provides a rationale for the inclusion of TE+FIN in multimodal therapeutic interventions intended to alleviate the musculoskeletal decline post-SCI.
我们曾报道过睾酮庚酸酯（TE）可预防脊髓损伤（SCI）后急性发生的肌肉骨骼衰退，但会导致前列腺体积增加近一倍。我们的目的是验证以下假设，即在我们的啮齿动物严重挫伤 SCI 模型中，给予 TE 加非那雄胺（FIN；II 型 5α-还原酶抑制剂）治疗不仅可预防慢性肌肉骨骼缺陷，而且不会引起前列腺增大。43 只 16 周龄雄性 Sprague-Dawley 大鼠接受以下处理：1）SHAM 手术（T 椎板切除术）；2）严重（250 kdyne）挫伤 SCI；3）SCI+TE（7.0mg/周，肌肉内）；或 4）SCI+TE+FIN（5mg/kg/天，皮下）。手术后 8 周，SCI 动物的血清睾酮和肛提肌/球海绵体肌（LABC）肌肉质量减少，TE 可预防这些变化。骨小梁和皮质（骨膜）骨转换（通过组织形态计量法评估）在 SCI 后升高，导致远端股骨骨小梁和皮质骨质量减少（通过微计算机断层扫描评估）。TE 治疗可使骨小梁和皮质骨转换正常化，并使骨小梁质量维持在 SHAM 动物的水平，但会导致前列腺增大。FIN 联合给药不能抑制 TE 诱导的肌肉骨骼作用，但可防止前列腺生长。两种药物方案均不能预防 SCI 引起的皮质骨丢失，尽管各组之间的整体骨强度没有差异。我们的研究结果表明，TE+FIN 可预防 SCI 动物的慢性骨小梁缺陷和 LABC 肌肉丢失，而不会引起前列腺增大，这为 TE+FIN 纳入旨在缓解 SCI 后肌肉骨骼衰退的多模式治疗干预提供了依据。
